Some authors have speculated that Anopheles mosquitoes may begin
transmitting malaria parasites (Plasmodium spp.) at higher altitudes in
the South American Andes because of climate change (1,2). In contrast,
highland malaria in Africa has more often been attributed to land use
alterations, malaria treatment resistance, changes in vector control
measures, and human migration into foothill and mountainous regions (3).
Before 2004, a short-lived epidemic of P. vivax malaria was recorded in
a village in Bolivia at an altitude of 2,300 m that was transmitted by
Anopheles pseudopunctipennis Theobald mosquitoes (4). Multiple
anopheline malaria vectors have also become established in the highlands
of Ecuador (5).

In this review, we summarize documented cases of highland malaria
that occurred in Ecuador during the early 20th century. We define the
term highland malaria to mean all malaria that occurs in regions with
steep topography. Using geographic information systems (ArcGIS version
10; ESRI, Redlands, CA, USA) and tabulated data from historical sources,
we reconstruct the geographic extent of malaria incidence during several
periods of interest. We also outline malaria control efforts and
attempts at malaria elimination for Ecuador during the 20th century and
at the beginning of the 21st century.

Malaria in Ecuador at the Beginning of the 20th Century

Although malaria was prevalent on the coast of Ecuador at the
beginning of the 20th century, it was considered by public health
officials to be a minor problem (6). Until 1908, Guayaquil on the coast
of Ecuador was affected by the constant menace of mosquitoes
transmitting yellow fever, and flea-borne bubonic plague reoccurred
regularly in all areas of the city and surrounding countryside (6-8).
Because Guayaquil had an image of being an unhealthy major port city,
officials in Ecuador signed an international sanitation convention in
1906 to combat outbreaks of yellow fever, bubonic plague, and cholera
(9). Under terms of the convention, officials were to take measures to
prevent ongoing transmission of these diseases, including the use of
mosquito screens on windows and doors of hospitals (9). During that
time, officials also experimented with the use of mosquito
larvae--eating fish as a biocontrol method in an attempt to control
yellow fever (8).

In 1908, the public health movement became active in Ecuador, and a
special sanitary commission was formed in Guayaquil (7,8). At that time,
malaria was still considered a minor health problem and many residents
allowed mosquitoes to bite them to provide them with long-term immunity
to malaria (10). Malaria prevention measures included bed nets, window
and door screens, and anopheline larval habitat destruction (8,10).
Several medical entomologists became active during this period in
Ecuador. These entomologists included the French entomologist Paul
Rivet, and the Ecuadorian entomologists F.R. Campos, Luis Leon, and J.
Rodriguez (11).

In 1919, many physicians in Ecuador began to receive training in
foreign countries, particularly in the United States through grants from
the Rockefeller Foundation, in an attempt to eliminate yellow fever and
malaria from Ecuador (6,8,12). With the elimination of yellow fever in
1920, attention inevitably turned to malaria, which still accounted for
a large percentage of deaths on the coast of Ecuador (13). By 1940,
malaria still remained a priority and was the second leading cause of
death in Ecuador after whooping cough (7). At the time, it was
recommended that a campaign against malaria should be initiated
throughout the entire country (7).

Highland Malaria during Construction of Guayaquil to Quito Railway
(1890-1945)

In 1886, construction began on the railway that was to link some of
the low-altitude regions of the country near Guayaquil to highland
regions and eventually Quito (altitude 2,800 m) (14). The railway was
constructed on a route that began in Guayaquil (at sea level), passed
through Milagro, and followed the valley bottom up toward Huigra, in
Chimborazo (altitude 1,250 m). After Huigra, the railway continued
higher toward Alausi, Chimborazo (altitude 2,340 m), after climbing the
infamous Devil's Nose switchbacks (14) (Figure 1).

When construction of the railway reached an elevation of 200 m,
workers reported bites from an unidentified bush-dwelling, flying insect
and many subsequently died of high fevers (15). At higher altitudes,
workers began to report fevers attributed to malaria (14). In 1906, the
Guayaquil newspaper Grito del Pueblo reported that railway workers
affected by fevers were removed from the construction site and brought
to the highland village of Chasqui, Pichincha, for recovery (16). The
following quotation from Daniel Barragan, one of the engineers for the
railway, provides strong evidence that mosquitoes (Culicidae) were
present at worksites: "The mosquitoes were our eternal companions,
during all of the night, their melodious and incessant humming many
times did not let us find sleep" (translated into English by
L.L.P.) (14).

Meitzner described treating many of the railway workers for malaria
during 1911 (10). In the winter of that year, the incidence of malaria
was so great among workers that construction halted completely (10).
Patients were usually brought to higher altitude towns such as Huigra
for treatment because there were insufficient medical facilities at
lower altitudes (10). Patients with malaria among the railway workers
were treated by Meitzner by using a combination of castor oil and
quinine and a diet that excluded meat (10). Before operation of the
railway, transportation between the coast and highland regions was
limited. Therefore, during the early operation of the railway to Quito,
the malaria parasite could have been repeatedly introduced by infected
passengers and workers to higher altitude regions, including the valleys
around the city of Quito (10).

[FIGURE 1 OMITTED]

The presence of malaria rather than other similar febrile illnesses
in railway workers is further supported by multiple collections of An.
pseudopunctipennis larvae (the highland malaria vector) in the
Chiripungo Valley, near Alausi, Chimborazo (altitude <2,400 m) (17).
As early as 1911, Meitzner made recommendations to railway engineers to
construct drainage ditches along the sides of the tracks to prevent
establishment of additional larval habitats in the pools that formed
there (10). Despite the efforts of Meitzner, An. pseudopunctipennis
mosquitoes remained in highland valleys of Chimborazo along the railway
at least into the mid 1940s. In 1943, Levi Castillo collected An.
pseudopunctipennis larvae along railway tracks up to an altitude of
1,250 m, and in 1944, he collected larvae in pools associated with
rivers in the towns of Huigra and Sibambe, Chimborazo (17). These
entomologic collections are consistent with the epidemiology of
continued malaria transmission; in 1944, a total of154 cases of malaria
among 864 residents were documented in Huigra (18). Aside from habitats
associated with the railway line, as shown in Figure 2, partial blockage
of the river below the newly built tracks along Devil's Nose would
probably have produced suitable pools for An. pseudopunctipennis larval
habitat.

Trains were a likely carrier for continued introduction of
anopheline mosquitoes into highland regions from the coast (17,19). At
Milagro station, adult mosquitoes were observed to fill train cars bound
for higher elevations (19). Levi Castillo found pools of water in
ceiling portions of trains, which served as mobile larval habitats for
anopheline mosquitoes (17). At higher elevations (>1,100 m), An.
pseudopunctipennis mosquitoes were documented as the sole vector,
although An. albimanus Wiedemann larvae were collected at lower
altitudes along the railway (18). Trains likely served to introduce
anopheline mosquitoes to highland regions until the 1960s and 1970s,
when the railway fell into disuse (15).

Highland Malaria Foci in Ecuador (1900-1950)

Malaria in highland regions of the northern Andes was not exclusive
to Ecuador and was found in Colombia in the Cauca, Manizales, Cali, and
Medellin Valleys, and in Peru in the Rimac, Urubamba, and
Laurin-Orcocota Valleys (20). Although malaria became more readily
studied and possibly more widespread in Ecuador during the 1940s, the
vector mosquito An. pseudopunctipennis was likely present for a much
longer period in highland regions (21). The malaria parasite is believed
to have been introduced to a handful of highland valleys in the 1800s
because there are no records of it before that time (22).

[FIGURE 2 OMITTED]

In 1905, students at the University of Guayaquil listed the
following highland valleys in Ecuador to which malaria was endemic:
Imbabura, Chota and Pinampiro valleys in Pichincha; Tumbaco and
Guayllabamba Valleys in Tungurahua; the Patate Valley; and the Yunguilla
Valley in Azuay (23) (Figure 1). All of these valleys except Patate were
regarded as regions to which malaria was endemic into the 1940s (24). In
almost every highland valley, Plasmodium vivax was implicated as the
only malaria parasite with An. pseudopunctipennis mosquitoes as vectors
(11,24).

Highland malaria was widespread in the early 1940s when it appeared
to reach its widest distribution (24). In addition to the valleys listed
above and highland valleys in Chimborazo associated with the railway,
malaria transmission was observed in Imbabura (Mira Valley and Salinas),
Pichincha (widespread in all highland valleys), Cafiar (all valleys at
an elevation <2,500 m), Chimborazo (Pallatanga Valley), Azuay
(Yunguilla Valley), and Loja (Catamayo Valley) (11,24) (Figure 1).

In 1938, Hanson and Montalvan documented a new epidemic of P. vivax
and P. falciparum malaria in Balzapamba, Bolivar (population 700), in an
orange-growing region at an elevation of 650 m (25) (Figure 1).
Residents had reportedly never experienced malaria until 1935, although
they lived near ([approximately equal to] 10 km away) the
malaria-endemic coastal plain. In 1935, an earthquake and associated
landslides diverted the course of the main river, and an open canal was
constructed to provide the town with drinking water (25). Throughout
their search, Hanson and Montalvan were able to locate only An.
pseudopunctipennis larvae in the open canal and in the algae-covered
pools, which formed on the edges of the newly-diverted river (25). This
epidemic highlights the scarcity of available larval habitat in steep
topography regions and the probable role of river pools and human-made
canals as habitat for anopheline larvae in highland regions.

Although An. albimanus mosquitoes have traditionally been
considered low-altitude (<300 m) vectors, they were identified as the
main malaria vector in an epidemic in the Yunguilla Valley in Azuay
(altitude [approximately equal to] 1,500 m) in the late 1940s (17,18).
An. pseudopunctipennis mosquitoes were collected from higher-altitude
towns in Azuay, such as Santa Isabel, during the 1940s (18). DDT was
just beginning to be used at that time in Ecuador and was successfully
applied in the 1940s to the Yunguilla Valley (19). During that time, 5%
DDT in a solution of kerosene was applied inside homes and to larval
habitats (26).

Little research was conducted in southern Ecuador, although there
were confirmed malaria cases in the Chota and Pinampiro Valleys in in
Imbabura; the Tumbaco and Guayllabamba Valleys in Pichincha; the Patate
Valley in Tungurahua; and the Yunguilla Valley in Azuay (18). Montalvan
reported his unconfirmed belief that the main vector in Catamayo might
be An. punctimacula Dyar mosquitoes, which were otherwise not implicated
in highland malaria transmission during the 1940s in Ecuador (18).
Similarly, there are few reports of malaria in highland parts of the
Amazonian side of the Andes during the early 20th century, likely
because the region was sparsely settled. Even in the lower altitude
Ecuadorian Amazon communities such as Puyo and Napo (presently Puerto
Napo) (altitude 700-900 m), the residents reported no cases of malaria
(27) (Figure 1).

Highland malaria in the northern valleys of Ecuador was well
documented during its most widespread period (1940-1950) (18,24).
Malaria was reported from valleys in Imbabura and Pichincha Provinces,
although it never reached the city of Quito (altitude 2,800 m) (24). On
the basis of valleys affected and maximum altitudes recorded for
anopheline species, the probable extent of highland malaria in the
northern valleys during its peak is shown in Figure 3.

Before the widespread occurrence of malaria in the 1940s,
Guayllabamba, Pichincha, was considered an area to which malaria was
endemic (18,21,22). Gradually, the vector and parasite spread to other
valleys, reaching Tingo and Alangasi by 1917 (21) (Figures 1, 3). The
spread of malaria may have been in part caused by an exodus of citizens
from Guayllabamba during the maximum incidence of the disease (28). When
malaria became more widespread in the 1940s, the government in Ecuador
brought in the US malariologist Henry Hanson, who identified An.
pseudopunctipennis mosquitoes as the only vectors (28). The maximum
altitude of the species was estimated to be 2,500 m-2,700 m, although
they have since been observed at 3,200 m (11,21,26). An.
pseudopunctipennis larvae were collected from clean, sunlit, rocky pools
associated with rivers, springs of water, irrigation ditches, and
hoof-prints from horses (17,18,20,21). Entomologists also noted a strong
larval association with spirogyra algae (18,21,26).

Although the expansion of Anopheles mosquito distribution is often
attributed to land use change, highland valleys of northern Ecuador have
been cleared and continuously farmed since pre-Colombian times (29). The
reported use of river edges as habitats also makes land use change
unlikely to be the sole explanation (17,18). Spread of the parasite and
vector may also be attributed to meteorologic causes, especially an
increase in minimum temperatures, which might otherwise limit parasite
or vector development. Increases of 0.5[degrees]C in average daily
temperature and 1.3[degrees]C in minimum nightly temperature were
observed in Quito during 1900-1930 (Figure 4). Therefore, meteorologic
factors may have caused the increased range of highland malaria before
1940.

[FIGURE 3 OMITTED]

A widespread campaign began in 1940 to eliminate malaria from
highland valleys of Pichincha and Imbabura (28). Malaria was eliminated
in the Los Chillos Valley by the Servicio Antipaludico del Valle de los
Chillos, led by Jaime Rivadeneira, and assisted by Carlos A. Marin and
Benjamin Wandemberg (11,17,21,24). A field laboratory was set up in San
Pedro de Tingo to lead an initial systematic larval habitat inspection
of the entire valley (21). All pools of water used by anopheline larvae
were drained by the construction of dikes and sprayed with crude oil
mixed with kerosene and occasionally DDT (17,21,28). Smaller pools were
filled with earth, and residents were provided with chemical repellent
for personal use (17,20). The campaign was deemed a success and malaria
did not return in subsequent years (21).

[FIGURE 4 OMITTED]

Human Colonization of Coastal Foothill Tropical Forests (1950-1970)

A map of malaria incidence published in 1950 shows the greatest
incidence in Ecuador to be in the northern coastal region and An.
albimanus, An. pseudopunctipennis, and An. punctimacula mosquitoes to be
the most common vectors (31). The foothills of the northern coast were
sparsely populated and land was not substantially developed before 1950,
because the region was covered in dense tropical forest with limited
access (32). However, roads were built linking Quito to the coast in the
late 1940s, and settlers moved into the region, forming Santo Domingo
(presently Santo Domingo de los Tsachiles) (altitude -500 m) (32).
Settlers converted wide swathes of forest to maize, rice, cocoa, and
coffee plantations for trade in Quito and in port cities (32). Seasonal
workers from the highlands migrated into the region to work during
summers (32). The first major epidemic of malaria was reported in 1958
(32). Land conversion likely provided sunlit habitat, which may have
been more suitable for some species of Anopheles mosquitoes. Also, the
immigration of large groups of highlanders lacking immunity likely
contributed to an epidemic in 1958 and to subsequent epidemics.

History of Malaria Elimination/Control Efforts in Ecuador

Although there were several regional public health organizations
addressing malaria on the coast of Ecuador, the National Institute of
Hygiene and Tropical Medicine Leopoldo Izquieta Perez was formed in 1940
(33). In 1944, Ecuador had the largest available hospital facilities of
any country in Latin America. Physicians were trained by the Pan
American Sanitary Bureau with funding from the Rockefeller Foundation,
and new public health laboratories were constructed (34,35). In 1948,
the Servicio Nacional Antimaldrico was formed to campaign against
malaria, especially on the coast, and to organize DDT spray operations
twice a year (22). In the early 1950s, US organizations led efforts to
eradicate malaria from malaria-endemic countries, although insecticide
resistance was beginning to appear and slow the eradication progress
(36). By 1956, Ecuador was considered to be in an early attack phase of
an eradication program (36).

After a recommendation from the Pan American Sanitation Committee,
the Sistema Nacional deEradicacion de Malaria (SNEM) was founded on July
21, 1956 (13,22). Its focus was to prevent insect-borne diseases through
vector control, mainly through use of chemical insecticides and larval
habitat elimination, and public education through school visits,
interviews, and community meetings (13). In addition to malaria, SNEM
has monitored and controlled Chagas disease, dengue fever,
onchocerciasis, yellow fever (in Amazonia), and leishmaniasis in Ecuador
(13).

Success of the SNEM in combating malaria has been closely
associated with its variable levels of funding. During 1957-1959,
dieldrin was sprayed inside houses on a continuous schedule, but was
regularly underdosed and therefore not effective (37). During 1961-1965,
DDT was applied to houses under the direction of the US Agency for
International Development (USAID) and the Pan American Health
Organization with greater success (37). Funding for medical entomology
research was so poor and unreliable that R. Levi Castillo, who had
previously documented many cases of highland malaria, renounced his post
at the University of Guayaquil and burned his books in protest (33). By
the late 1960s, USAID funding had decreased substantially, resulting in
a subsequent epidemic (37). Azuay and Caiar, and to a lesser extent
Pichincha and Chimborazo, had a small increase of malaria cases in
low-lying valleys (Figure 5). Similarly, in 1969 during another peak
year, these highland provinces and most areas of the coast of Ecuador
were affected by malaria (Figure 6, panel A).

USAID funding was reinstated in 1973 through a reinvestment with
the SNEM (22,37). However, by 1980, the SNEM was considered operational
and no longer relied on international funding (37). During an assessment
in 1983, the SNEM was deemed to be a capable department but with some
financial concerns, such as having an aging fleet of boats and jeeps,
and a residual house spray schedule of 3 times a year rather than the
recommended 4 times (37).

Through the latter half of the 1980s, some malaria cases were
reported in highland provinces of Pichincha, Cotopaxi, Bolivar, and to a
lesser extent, Chimborazo and Loja (Figure 5). Tungurahua, Carchi, and
Imbabura Provinces reported only occasional malaria cases (Figure 5).
During 1 of the peak years (1990), there was widespread malaria along
the coast, in Amazonia, and in highland provinces (although perhaps only
in lower-altitude regions of these provinces) (Figure 5; Figure 6, panel
B). Again in 2000, widespread malaria was observed in the coastal and
Amazonian areas of Ecuador (Figure 6, panel C), but only Pichincha and
to a lesser extent Cotopaxi and Bolivar observed an increase in cases in
the highlands (Figures 5, 6). However, despite occasional cases of
malaria, the SNEM reported a steady decrease in malaria in Ecuador
during the past 20 years, likely as a response to efforts of various
programs that have been more recently implemented in the country (13).

[FIGURE 5 OMITTED]

Conclusions

Malaria became more widespread in northern highland regions of
Ecuador during 1900-1940 but was subsequently eliminated from these
regions through habitat elimination and use of chemical insecticides
(21). In Chimborazo during 1900-1950, malaria spread into highland
valleys along the railway linking Guayaquil and Quito (10,17,18).
Although there have likely been a few highland epidemics since the
1940s, only 1 report in 1991 documented the presence of An.
pseudopunctipennis mosquitoes in river-associated habitats of
Guayllabamba (28). To effectively monitor establishment of highland
malaria vectors, a focus on historically malaria-endemic highland
valleys may be needed. Anopheline habitats in areas with steep
topography are expected to differ from those in flat, low-altitude
regions. Therefore, these differences will necessitate further study of
local dynamics of mosquito ecology, meteorologic variables, and
transmission cycles.

This study was supported by a Natural Sciences and Engineering
Research Council of Canada discovery grant to F.F.H., an International
Development Research Centre doctoral research award to L.L.P., and a
Natural Sciences and Engineering Research Council of Canada postgraduate
scholarship to L.L.P.

Dr Pinault just completed her doctorate at Brock University,
Canada, studying the ecology of highland Anopheles spp. in the Andes in
Ecuador. Her primary research interests include highland malaria, vector
ecology, spatial ecology with geographic information systems, and human
perspectives of vector-borne diseases.

Dr Hunter is a medical entomologist and professor in the Department
of Biological Sciences, Brock University, Canada. Her primary research
interests include behavioral and feeding ecology of biting flies,
entomologic monitoring for public health, and molecular and chromosomal
systematics of Anopheles spp. mosquitoes.

(13.) Espinoza Lopez N, Trivifio Yepez L, Alarcon y Alvarado J,
Velez Nieto L. Technical report: historical and current contribution of
the national control of vector-borne disease service (SNEM) for the
betterment of the health and the quality of life of Ecuadorians in
relation to the illnesses transmitted by arthropod vectors, period
1956-2008 [in Spanish]. Guayaquil (Ecuador): SNEM Technical Commission,
Ministry of Public Health, Government of Ecuador; 2009.

(14.) Garcia Idrovo G. The most difficult railway in the world [in
Spanish]. Quito (Ecuador): Ministry of Culture, Government of Ecuador;
2008.

(30.) Summary of the meteorological observations made in the
observatory and in the diverse stations of the Republic [in Spanish].
Quito (Ecuador): Astronomical and Meteorological Observatory of Quito,
Ministry of Public Instruction, Government of Ecuador; 1929-1937; 1937.